Injury, congenital abnormalities, disease and aging result in disorders of organs and tissues. Organ transplantation yields a high risk of rejection, even with a good histocompatibility match. Immunosuppressive drugs such as cyclosporin and FK506 are usually given to the patient to prevent rejection. However, these immunosuppressive drugs have a narrow therapeutic window between adequate immunosuppression and toxicity. Prolonged immunosuppression can weaken immune systems, which can lead to a threat of infections developing. In some instances, even immunosuppression is not enough to prevent organ rejection. Therefore, current reconstruction techniques prefer using native tissues from multiple body sites. Nonetheless, many complications are associated with the use of native non-autologous tissues.
In an attempt to avoid these problems various methods have been reported in which the patients own autologous cells have been cultured in vitro. For example, U.S. Pat. No. 5,429,938 issued to Humes, describes a method of reconstructing renal tubules using cultured kidney cells. The reconstructed renal tubules can be implanted into the patient.
Naughton et al. disclosed a three-dimensional tissue culture system in which stromal cells are laid over a polymer support system (see U.S. Pat. No. 5,863,531) and parenchyma cells are cultured on the stromal matrix. Vacanti et al. have also disclosed methods for culturing cells in a three-dimensional matrix made of a biodegradable polymer.
A current barrier in the formation of tissues is an adequate vascular supply. Because the nutrition to the cells by diffusion can only penetrate the surface of tissues, neovascularization is a requirement for any solid tissue larger than a few cubic millimeters (Mooney et al. (1999) Sci Am. 280(4):60-65). Cells within a bioengineered organ or at the center of an injected cell mass need an extensive blood vessel network to supply nutrients and oxygen and remove waste products. Many techniques have been used to attempt to circumvent this obstacle. Cells have been seeded and grown on micro-porous frameworks as well as scaffolds etched with mini networks imitating vascular systems. However, the slow process of native blood vessels naturally invading the transplanted tissue is not always sufficient for adequate graft survival.
There exists a need for better methods and compositions capable of increasing and stimulating rapid vascularization into a surgical site. In particular, new compositions capable of modulating angiogenesis and stimulating tissue formation would satisfy a long-felt therapeutic need.